We have recently developed a new method, termed bioautography, that enables one to visualize a large number of new isozymes which could not be studied by any other approach. The principle of bioautography involves the visualizaton of mammalian isozymes by employing mutant bacteria as specific "staining" reagents. As in the case of recombinant DNA technology, bioautography permits one to employ a powerful bacterial genetics approach in the study of problems peculiar to mammalian genetics. The bioautographic studies proposed here present simple and rapid approaches to a host of important problems in somatic cell genetics and human genetics. Since bioautography is itself a biochemical selection procedure for bacterial auxotrophs, bioautography is ideally suited to the study of the enzymes involved in potential or existing mammalian auxotrophic mutants. Hence, we will devise bioautographic assays in order to further develop several genetic systems which have been shown to be biochemically selectible in cultured cells. Emphasis will be given to genetic systems that display regulatory phenomena. First, we will use bioautography to study two mutations that result in enzyme over-production in cultured cells; i.e., dihydrofolate reductase and aspartate transcarbamylase. In the case of enzyme over-production mutants, we will ask whether the enzyme in mutant cells has the same electrophoretic mobility and isoelectric point as the enzyme in wild type cells. Second, we will use bioautography to study several luxury enzymes which are the basis of biochemical selection systems for certain differentiated cell types; i.e., glutamine synthetase, phenylalanine hydroxylase, and tyrosine hydroxylase. Bioautography will be employed in the study of the above enzymes in mutant and hybrid cells. Lastly, bioautography will be used as a tool to map to human chromosomes several genes that could not be mapped by any other method.